Enantioselective Construction of Secondary Boronic Esters

Significance

The method adresses the difficult problem of the preparation of secondary organo­boron derivatives. In general, the hydroboration of 1,2-disubstituted alkenes suffers from low regio­selectivity. Using an enantioselective Rh(I)/bis-phosphine catalytic hydrogenation, vinyl boronates 1 were transformed into chiral secondary boronic esters. The starting vinyl boronates were prepared from the alkyne by hydrobromination with BBr₃ and subsequent transmetallation of the lithiated alkene to the borate with (pin)BOi-Pr. A variety of functional groups were tolerated under the mild reaction conditions. Importantly, examples 2c and 2f, bearing a pre-existing stereocenter, show that the reaction is reagent-controlled. Using the reported method, versatile secondary boronic esters can be accessed that are not available from other catalytic systems. Further derivatization of the boronic esters 2 was accomplished in situ by the preparation of chiral amine 3 and chiral alcohol 4.